Hereditary renal amyloidosis with a variant lysozyme p.Trp82Arg in a Chinese family: case report and literature review

Abstract

Background Lysozyme amyloidosis is a rare hereditary systemic amyloidosis with amyloid deposits in various tissues leading to progressive organ failure. It has been mainly reported in developed countries since 1993. Here we report a lysozyme amyloidosis family with variant lysozyme p.Trp82Arg in a Chinese family. Case presentation The main clinical manifestation of this case was dominant kidney involvement presenting with proteinuria and decreased renal function. Biopsy of the kidney showed massive amyloid deposits in the glomerular mesangium and subendothelium. Immunohistochemistry and mass spectrometry of renal tissue confirmed the lysozyme nature of the amyloid. DNA sequencing of the peripheral blood leukocytes revealed a single base-pair transition from T to C (TGG/ CGG) of codon 82, leading to the replacement of tryptophan by arginine in the mature protein (p.Trp82Arg). The affected patients in this family also presented with dominant kidney involvement, one of them has been confirmed by IHC and mass spectrometry on his renal biopsy and gene testing as well. As there is no radical therapy for lysozyme amyloidosis, patients were given symptomatic treatment such as antihypertensive drugs and antibiotics. To our knowledge, this is the first report of lysozyme amyloidosis in a Chinese family. Conclusions Hereditary amyloidosis with a variant lysozyme of p.Trp82Arg presented with dominant kidney involvement was firstly reported in a Chinese family.

Lysozyme amyloid: evidence for the W64R variant by proteomics in the absence of the wild type protein

“…A similar case of W64R lysozyme amyloid has just been reported by Li et al. [ 4 ]. Although the genetic sequencing showed the presence of the mutation, the proteomics output confirmed the presence of lysozyme, but details on fibrils composition were not provided.…”

A Pilot Study of Rare Renal Amyloidosis Based on FFPE Proteomics

“…Alys is a type of hereditary amyloidosis that is extremely rare in clinical practice, first described in 1993 by Pepys et al [ 31 ]. It is so rare that only about thirty families have been noted across the world [ 10 ]. The hereditary amyloidosis was usually caused by genetic mutations that lead to amino acid mutations in the encoded protein, which affect the three-dimensional structure of the protein and its interaction with other proteins, forming amyloid deposits [ 19 , 22 ].…”

“…The diagnosis and treatment of Alys are significantly different from other types, which directly affect the prognosis. Liver or kidney transplantation may be useful as a palliative method for patients with spontaneous liver rupture or renal failure [ 10 ]. Proteomics can directly detect pathogenic amyloid fibrin precursors and accurately type hereditary amyloidosis, while traditional IHC technology often cannot type for lack of hereditary amyloidosis antibody.…”

“…Hereditary or familial amyloidosis is another group including fibrinogen Aα chain, transthyretin (TTR), apolipoprotein A-I and apolipoprotein A-II, lysozyme, gelsolin and cystatin C [ 6 , 7 ]. Renal amyloidosis cases are predominantly AL and ALECT2 amyloidosis, but sometimes rare hereditary or familial amyloidosis are also found to be involved in the renal pathogenesis [ 8 , 9 , 10 ]. Immunoglobulin (Ig) light chain (LC) amyloidosis (AL) is characterized by an abnormal extracellular deposition of a monoclonal Ig LC protein of either lambda (λ) or kappa (κ) isotype [ 11 ].…”

An Historical Overview of the Amyloidoses

“…Since 1990, several other molecules with mutations that predispose to misfolding have been discovered as rare causes of amyloidosis. These include hereditary renal amyloidosis due to mutations in lysozyme [58] giving rise to ALys Amyloidosis; mutations in fibrinogen, giving rise to AFib amyloidosis [59] apolipoproteins AI, giving rise to AApoAI amyloidosis; mutations in Apolipoprotein AII, giving rise to AApoAII amyloidosis [60]; mutations in the protein gelsolin, giving rise to AGel amyloidosis [61].…”